Stage 4 RET-rearranged lung cancer: complete pathologic response to pralsetinib

What happened, in summary

A 66-year-old never-smoking woman developed shortness of breath, productive cough, and chest pain. CT showed a 35 × 30 mm mass in the left upper lung with enlarged mediastinal and hilar lymph nodes, massive left pleural fluid, and left pleural nodules. Thoracentesis found malignant cells in the pleural fluid, confirming pleural involvement. PET/CT showed high uptake in the lung mass, pleural nodules, and mediastinal and hilar lymph nodes. Biopsy of the lung mass showed poorly differentiated adenocarcinoma that was CK7-positive, TTF-1-positive, Ki-67 70%, and PD-L1-negative. Next-generation sequencing of lung tissue and pleural effusion identified a KIF5B-RET rearrangement in both samples, along with a TP53 missense mutation and low tumor mutation burden. She was diagnosed with Stage IV, T2aN2M1a RET-rearranged lung adenocarcinoma and started pralsetinib 400 mg once daily. After 2 months, the lung tumor shrank to 17 × 12 mm and the pleural effusion disappeared, meeting partial response criteria. Because of decreased exercise tolerance and grade 2 leukopenia, the pralsetinib dose was gradually reduced to 200 mg once daily. After 7 months, pleural nodules were no longer visible on CT, and PET/CT showed no FDG uptake in the left pleura or N2 lymph nodes. She then underwent left upper apical and posterior segment resection with pleural nodule and lymph-node dissection. Pathology showed no residual viable tumor in the primary site, pleural nodules, or sampled lymph nodes, confirming complete pathologic response. She continued pralsetinib 200 mg daily as postoperative adjuvant therapy. This combined targeted therapy and surgery strategy converted radiographic metastatic disease to a pathologic complete response while maintaining postoperative RET-directed treatment.